(3E,5E)-3,5-bis(2-bromobenzylidene)-1-methylpiperidin-4-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3E,5E)-3,5-bis(2-bromobenzylidene)-1-methylpiperidin-4-one
• 英文别名: 3,5-bis((E)-2-bromobenzylidene)-1-methylpiperidin-4-one；(3E,5E)-3,5-bis[(2-bromophenyl)methylidene]-1-methylpiperidin-4-one
• 化学式: C₂₀H₁₇Br₂NO
• 分子量: 447.169
• InChiKey: FAVOOEYXDNBGBH-OTYYAQKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3E,5E)-3,5-bis(2-bromobenzylidene)-1-methylpiperidin-4-one 、 噻莫西酸 、 苊醌 以 甲醇 为溶剂， 反应 3.0h， 以90%的产率得到spiro[5.2'']acenaphthene-1''-onespiro[6.3']-5'-(2-bromophenylmethylidene)-1'-methylpiperidin-4'-one-7-(2-bromophenyl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole
  参考文献：
  名称：

  An atom economic synthesis and AChE inhibitory activity of novel dispiro 7-aryltetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole and 4-aryloctahydroindolizine N-methylpiperidin-4-one hybrid heterocycles

  摘要：

  The 1,3-dipolar cycloaddition of azomethine ylides generated in situ from acenaphthenequinone and alpha-amino acids viz. 1,3-thiazolone-4-carboxylic acid and piperidine-2-carboxylic acid to a series of 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones afforded novel spiro[5.2 '']acenaphthene-1 ''-onespiro[6.3']-5'-arylmethylidene-1'-methylpiperidin-4'-one-7-aryltetrahydro-1H-pyrrolo[12-c][1,3]thiazoles and spiro[2.2 '']acenaphthene-1 ''-onespiro[3.3']-5'-arylmethylidene-1'-methylpiperidin-4'-one-4-aryloctahydroindolizines respectively in quantitative yields. These compounds were evaluated for their AChE inhibitory activity and compound 3c was found to be the most potent with IC50 1.86 mu mol/L. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.050
• 作为产物：
  描述：

  N-甲基-4-哌啶酮 、 邻溴苯甲醛 在 barium(II) hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 (3E,5E)-3,5-bis(2-bromobenzylidene)-1-methylpiperidin-4-one
  参考文献：
  名称：

  正确取代的环状双-（2-溴亚苄基）化合物作为双重 p300/CARM1 抑制剂并诱导癌细胞凋亡

  摘要：

  双-（3-溴-4-羟基）亚苄基环状化合物已被我们报道为表观遗传多重配体，但两翼的不同取代提供了具有选择性抑制的类似物。由于 1-benzyl-3,5-bis((E)-3-bromobenzylidene)piperidin-4-one 3 显示双重 p300/EZH2 抑制与肿瘤细胞组和体内异种移植中的癌症选择性细胞死亡有关模型，我们制备了一系列双（（E）-2-溴亚苄基）环状化合物 4a–n 以测试生化（p300、PCAF、SIRT1/2、EZH2 和 CARM1）和细胞（NB4、U937、MCF-7 , SH-SY5Y) 检测。大多数 4a-n 表现出有效的双重 p300 和 CARM1 抑制，有时达到亚微摩尔水平，并主要在测试的白血病细胞系中诱导细胞凋亡。在酶和细胞检测中最有效的化合物在 N1 位带有一个 4-哌啶酮部分和一个甲基 (4d)、苄基 (4e) 或酰基 (4k-m) 取代基。苄基部分延长为

  DOI：

  10.3390/molecules25143122

文献信息

• Anti-infective compounds
  申请人：Brodin Priscille

  公开号：US20110178077A1

  公开（公告）日：2011-07-21

  The present invention relates to small molecule compounds and their use in the treatment of bacterial infections, in particular Tuberculosis.

  本发明涉及小分子化合物及其在治疗细菌感染，特别是结核病方面的用途。
• New MD2 inhibitors derived from curcumin with improved anti-inflammatory activity
  作者：Yali Zhang、Zhiguo Liu、Jianzhang Wu、Bin Bai、Hongjin Chen、Zhongxiang Xiao、Lingfeng Chen、Yunjie Zhao、Hazel Lum、Yi Wang、Hong Zhang、Guang Liang

  DOI：10.1016/j.ejmech.2018.02.008

  日期：2018.3

  An overactive Toll-like receptor (TLR) signaling complex is a significant pathogenic factor of acute and chronic inflammatory diseases. The natural product curcumin is reported to inhibit the TLR4 co-receptor, MD2 (myeloid differentiation protein 2), but its low in vivo bioavailability limits its therapeutic potential. We developed new curcumin analogs (MACs) with removal of the beta-diketone moiety and substituted residues in benzene rings, and identify these as potential MD2 inhibitors with improved inhibition potency and stability over that of curcumin. Specifically, MAC 17 and 28 showed the highest anti-inflammatory activity, with >90% inhibition of LPS-stimulated cytokine secretion from macrophages, and protected against LPS-induced acute lung injury and sepsis. The MACs inhibited the TLR4-MD2 signaling complex through competition with LPS for binding on MD2, likely at Arg(90). Our findings indicated that MAC 17 and 28 are promising candidates for future development as therapeutic drugs for inflammatory diseases with an endotoxin etiology. (C) 2018 Elsevier Masson SAS. All rights reserved.
• Synthesis and anti-tumor activity of EF24 analogues as IKKβ inhibitors
  作者：Rong Jin、Qiuxiang Chen、Song Yao、Encheng Bai、Weitao Fu、Ledan Wang、Jiabing Wang、Xiaojing Du、Tao Wei、Haineng Xu、Chengxi Jiang、Peihong Qiu、Jianzhang Wu、Wulan Li、Guang Liang

  DOI：10.1016/j.ejmech.2017.11.077

  日期：2018.1

  EF24 is an IKK beta inhibitor (IC50: 72 mu M) containing various anti-tumor activities. In this study, a series of EF24 analogs targeting IKK beta were designed and synthesized. Several IKK beta inhibitors with better activities than EF24 were screened out and B3 showed best IKK beta inhibitory (IC50: 6.6 mu M). Molecular docking and dynamic simulation experiments further confirmed this inhibitory effect. B3 obviously suppressed the viability of Hela229, A549, SGC-7901 and MGC-803 cells. Then, in SGC-7901 and MGC-803 cells, B3 blocked the NF-kappa B signal pathway by inhibiting IKK beta phosphorylation, and followed arrested the cell cycle at G2/M phase by suppressing the Cyclin B1 and Cdc2 p34 expression, induced the cell apoptosis by down-regulating Bcl-2 protein and up-regulating cleaved-caspase3. Moreover, B3 significantly reduced tumor growth and suppressed the IKK beta-NF-kappa B signal pathway in SGC-7901 xenograft model. In total, this study present a potential IKK beta inhibitor as anti-tumor precursor. (C) 2017 Published by Elsevier Masson SAS.
• US8785452B2
  申请人：——

  公开号：US8785452B2

  公开（公告）日：2014-07-22
• Properly Substituted Cyclic Bis-(2-bromobenzylidene) Compounds Behaved as Dual p300/CARM1 Inhibitors and Induced Apoptosis in Cancer Cells
  作者：Rossella Fioravanti、Stefano Tomassi、Elisabetta Di Bello、Annalisa Romanelli、Andrea Maria Plateroti、Rosaria Benedetti、Mariarosaria Conte、Ettore Novellino、Lucia Altucci、Sergio Valente、Antonello Mai

  DOI：10.3390/molecules25143122

  日期：——

  cells and in in vivo xenograft models, we prepared a series of bis((E)-2-bromobenzylidene) cyclic compounds 4a–n to test in biochemical (p300, PCAF, SIRT1/2, EZH2, and CARM1) and cellular (NB4, U937, MCF-7, SH-SY5Y) assays. The majority of 4a–n exhibited potent dual p300 and CARM1 inhibition, sometimes reaching the submicromolar level, and induction of apoptosis mainly in the tested leukemia cell lines

  双-（3-溴-4-羟基）亚苄基环状化合物已被我们报道为表观遗传多重配体，但两翼的不同取代提供了具有选择性抑制的类似物。由于 1-benzyl-3,5-bis((E)-3-bromobenzylidene)piperidin-4-one 3 显示双重 p300/EZH2 抑制与肿瘤细胞组和体内异种移植中的癌症选择性细胞死亡有关模型，我们制备了一系列双（（E）-2-溴亚苄基）环状化合物 4a–n 以测试生化（p300、PCAF、SIRT1/2、EZH2 和 CARM1）和细胞（NB4、U937、MCF-7 , SH-SY5Y) 检测。大多数 4a-n 表现出有效的双重 p300 和 CARM1 抑制，有时达到亚微摩尔水平，并主要在测试的白血病细胞系中诱导细胞凋亡。在酶和细胞检测中最有效的化合物在 N1 位带有一个 4-哌啶酮部分和一个甲基 (4d)、苄基 (4e) 或酰基 (4k-m) 取代基。苄基部分延长为